This application is in the area of polymers for biomedical applications, and in particular describes polymers that can be used as immunoadjuvants.
Vaccine Development
A wide variety of antigens stimulate the production of antibodies in animals and confer protection against subsequent infection. However, some antigens are unable to stimulate an effective immune response.
The immunogenicity of a relatively weak antigen is often enhanced by the simultaneous administration of the antigen with an adjuvant, a substance that is not immunogenic when administered alone, but will induce a state of mucosal and/or systemic immunity when combined with the antigen. It has been traditionally thought that adjuvants, such as mineral oil emulsions or aluminum hydroxide, form an antigen depot at the site of injection that slowly releases antigen. Recent studies by Allison and Byars, in: "Vaccines: New Approaches to Immunological Problems":, R. W. Ellis, ed., p. 431, Butterworth-Heinemann, Oxford (1992) indicate that adjuvants enhance the immune response by stimulating specific and sometimes very narrow branches of the immune response by the release of cytokines. Unfortunately, many immunoadjuvants, such as Freund's Complete Adjuvant, are toxic and are therefore only useful for animal research purposes, not human vaccinations. Freund's Complete Adjuvant contains a suspension of heat-killed Mycobacterium tuberculosis in mineral oil containing a surfactant and causes granulomatous lesions in animals at the site of immunization. Freund's adjuvant may also cause the recipient of a vaccine to test positive for tuberculosis. Some synthetic polyelectrolytes have been found to provide immunostimulation when combined with an antigen. For example, the adjuvant activity of polyacrylic acid (PAA), copolymers of acrylic acid and N-vinylpyrrolidone (CP-AA-VPD), poly-2-methyl-5-vinyl pyridine (PMVP), poly-4-vinyl-N-ethylpyridinium bromide (PVP-R.sub.2) and similar compounds, when conjugated to an antigen, has been studied by Petrov et. al., Jhurnal Vses. Khim. Ob-va im. D. I. Mendeleeva, 33:22-42 (1988). The immunomodulatory effect of polyelectrolyte complexes containing many of these same polyelectrolytes has also been more recently reviewed by Petrov, et al., Sov. Med. Rev. D. Immunol., 4:1-113 (1992). However, the toxicity and biodegradability of these polymers has not been studied and may prevent use of these polymers as adjuvants for use in humans.
A non-toxic adjuvant or carrier having the ability to stimulate an immune response to non-antigenic or weakly antigenic molecules would be useful in the development and administration of vaccines.
Therefore, it is an object of the present invention to provide an adjuvant that can be safely administered to humans and animals with minimal toxicity.
It is a further object of the present invention to provide an adjuvant that is soluble and biodegradable.
It is a further object of the present invention to provide a vaccine that confers protection against an organism such as the influenza virus or Clostridium tetani bacteria.
It is a further object of the present invention to provide a rapid and efficient method of synthesizing a polymer, such as polyphosphazene, for use as an adjuvant.